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. 2021 Aug 25;40:268. doi: 10.1186/s13046-021-02072-9

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Knockdown of VIRMA attenuates the malignant phenotype in vivo. A – Macroscopic view of tumor formation (in ovo and ex ovo) and neo-angiogenesis in NCCIT scramble and VIRMA knockdown experimental conditions. Notice reduced size and decreased number of vessels in VIRMA knockdown tumors; B and C – Distribution of macroscopic tumor size and number of peri-tumor vessels (normalized to size of tumor) in scramble and VIRMA knockdown conditions; D – Histological aspects of scramble and VIRMA knockdown tumors. Notice the highly vascularized tissue around the scramble tumor, and infiltration of individual clusters of tumor cells around and into blood vessels (black box inset). Notice the cellular atypia (red box inset), including mitotic figure (blue arrow), in a more cellular area. The two VIRMA knockdown tumors with higher tumor cellularity are also shown (notice the clear cellular atypia, with prominent nucleoli and mitotic figures – blue arrows – including an atypical tripolar mitosis); E and F - Distribution of tumor size and number of peri-tumor vessels assessed histologically in scramble and VIRMA knockdown conditions; G – Presence of images of invasion into blood vessels. * p < 0.05; ** p < 0.01; *** p < 0.001